Metabolism of articular cartilage proteoglycans in vitro : effects of synovial membrane products and mechanical pressure

The effect of synovial membrane products and mechanical pressure upon the metabolism of articular cartilage proteoglycans has been studied in vitro. The degradation of cartilage proteoglycans was studied in an organ culture system and measured as the release of [35S ] sulphate from prelabelled cartilage. The effect of synovial membrane products upon the synthesis of proteoglycans was studied in a chondrocyte monolayer system and the effect of mechanical pressure upon the synthesis of proteoglycans in an organ culture system. In both types of experiments [35S] sulphate was used as precursor. The findings may be summarized as follows 1 Conditioned synovial medium (control-SM) enhanced the degradation and reduced the synthesis of cartilage proteoglycans. In addition the degradation was further enhanced when the synovial tissue had been cultured in the presence of dextran sulphate. 2 Conditioned medium from synovial tissue cultured in the presence of indo-methacin (indo-SM), significantly reduced the synthesis of cartilage proteoglycans in chondrocyte cultures and reduced, although non-significantly, the degradation of proteoglycans in whole cartilage cultures. 3 Addition o f the prostaglandins E1 or E2 (PGE1 or PGE2 ) together with indo-SM to the cartilage cultures greatly enhanced cartilage degradation whereas the addition of PGE1 or PGE2 together with control-SM had no effect compared with that of control-SM alone. 4 Conditioned medium from synovial tissue cultured in the presence of low doses of glucocorticoids reduced cartilage degradation compared with control-SM. However, addition of control-SM together w ith low concentrations of glucocorticoids to the cartilage cultures significantly enhanced cartilage degradation. 5 Conditioned medium from synovial tissue cultured with actinomycin D or cycloheximide did not enhance cartilage degradation compared with cartilage cultured alone. 6 A continuous pressure of approximately 30 kgfcm-2 on cultures of cartilage reduced both the synthesis and the degradation o f cartilage proteoglycans. Although it is difficult to extrapolate from the in vitro to the in vivo situation, it is proposed that some factor(s) from the synovial membrane have the capacity to enhance the degradation and reduce the synthesis o f articular cartilage proteoglycans. From these experiments it cannot be completely excluded that treatm ent of arthritic joints with non-steroidal or streroidal anti-inflammatory drugs may result under certain conditions in enhanced joint damage. It is also suggested that under certain conditions the metabolism o f cartilage proteoglycans could be directly affected by mechanical stress.Diss. Umeå, Umeå universitet, 1982, härtill 6 uppsatserdigitalisering@um